J Cancer 2014; 5(6):425-432. doi:10.7150/jca.8594

Research Paper

ERCC1, XRCC1 and GSTP1 Single Nucleotide Polymorphisms and Survival of Patients with Colon Cancer Receiving Oxaliplatin-Based Adjuvant Chemotherapy

Aziz Zaanan1,2,3,4,5✉, Cécile Dalban6, Jean-François Emile7,8, Hélène Blons4,9, Jean-François Fléjou1,2,10, Claire Goumard1,2, Melek Istanbullu1,2, Claire Calmel1,2, Khalid Alhazmi 11, Pierre Validire12, Christophe Louvet13, Aimery de Gramont14, Pierre Laurent-Puig4,5,9, Julien Taïeb3,4,5, Françoise Praz1,2✉

1. INSERM, UMR_S 938, Saint-Antoine Research Centre, F-75012, Paris, France;
2. UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre, F-75012, Paris, France;
3. Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, AP-HP, Paris, France;
4. Paris Sorbonne Cité, University of Paris Descartes, Paris, France;
5. Cancer Research Personalized Medicine (CARPEM), European Georges Pompidou Hospital, AP-HP, Paris, France;
6. Department of Biostatistics and Epidemiology, EA4184, Georges François Leclerc Center, Dijon, France;
7. Department of Pathology, Ambroise Paré Hospital, AP-HP, Boulogne, France;
8. EA4340, University of Versailles, Saint-Quentin-en-Yvelines, Versailles, France;
9. Department of Biology, European Georges Pompidou Hospital, AP-HP, Paris, France;
10. Department of Pathology, Saint-Antoine Hospital, AP-HP, Paris, France;
11. Department of Pathology, European Georges Pompidou Hospital, AP-HP, Paris, France;
12. Department of Pathology, Mutualiste Montsouris Institute, Paris, France;
13. Department of Medical Oncology, Mutualiste Montsouris Institute, Paris, France;
14. Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, Paris, France.

Abstract

Background: While single nucleotide polymorphisms (SNP) in genes involved in DNA repair or drug metabolism have been shown to influence survival of metastatic colon cancer patients treated with FOLFOX, data on adjuvant setting are scarce.

Methods: This study evaluated the correlation between disease-free survival (DFS) of 210 unselected stage III colon cancer patients receiving FOLFOX chemotherapy, and ERCC1-118 (rs11615, c.354T>C), XRCC1-399 (rs25487, c.1196G>A) and GSTP1-105 (rs1695, c.313A>G) polymorphisms. SNP were determined on tumor DNA using a PCR-based RFLP technique.

Results: In univariate analysis, a trend towards longer DFS was observed for ERCC1 (C/T + T/T) versus (C/C) (HR=2.29; p=0.06), and XRCC1 (A/A) versus (G/G + G/A) (HR=1.61; p=0.16), but not for GSTP1 genotypes; a statistically significant p value was obtained when combining ERCC1 and XRCC1 favorable genotypes (0 versus ≥ 1 favorable genotypes, HR=2.42; p=0.02). After adjustment on tumor stage, lymph node ratio and differentiation grade, multivariate analysis showed that combining ERCC1 and XRCC1 genotypes gave a p value slightly above the threshold for statistical significance (HR=2.03; p=0.06), which was lower than for tumor stage, lymph node ratio or differentiation grade.

Conclusion: The association of ERCC1 and XRCC1 polymorphisms may influence the prognosis of stage III colon cancer patients treated with FOLFOX adjuvant chemotherapy. Yet, these findings need to be confirmed in independent prospective studies.

Keywords: colon cancer, adjuvant FOLFOX, polymorphism, ERCC1, XRCC1, GSTP1.

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How to cite this article:
Zaanan A, Dalban C, Emile JF, Blons H, Fléjou JF, Goumard C, Istanbullu M, Calmel C, Alhazmi K, Validire P, Louvet C, de Gramont A, Laurent-Puig P, Taïeb J, Praz F. ERCC1, XRCC1 and GSTP1 Single Nucleotide Polymorphisms and Survival of Patients with Colon Cancer Receiving Oxaliplatin-Based Adjuvant Chemotherapy. J Cancer 2014; 5(6):425-432. doi:10.7150/jca.8594. Available from http://www.jcancer.org/v05p0425.htm